Profile of Select Hepatic Insulin Signaling Pathway Genes in Response to 2-Aminoanthracene Dietary Ingestion

Some genes that regulate various processes such as insulin signaling, glucose metabolism, fatty acid and lipid biosynthesis were profiled. The objective of the current investigation is to examine the mRNA expression of some genes that mediate insulin signaling due to 2AA toxicity. 2AA is a polycyclic aromatic hydrocarbon (PAHs) that has been detected in broiled food and tobacco smoke. Twenty four post-weaning 3-4 weeks old F344 male rats were exposed to 0mg/kg-diet, 50mg/kg-diet, 75mg/kg-diet and 100mg/kg-diet 2AA for 2-weeks and 4-weeks. The mRNA expression of akt1, g6pc, gck, glut4, insr, irs1, pp1r3c, pampk, socs2, and srebf1 was determined by qRTPCR followed by the quantification of g6pc and ampk via ELISA. Results seem to suggest 2AA modulates these genes depending on the length of exposure. Up-regulation of ampk and socs2 genes in animals treated with 100mg/kg-diet and 50mg/kg-diet respectively during 14 days of feeding was noted. G6pc expression seems to be inhibited in the 2-weeks group while dose-dependently increased in the 4-weeks group. Hepatic activity of g6pc was enhanced significantly in the livers of rats that ingested 2AA. It appears 2AA intoxication leads to the activation of irs1 and akt1 genes in the liver. Quantified ampk amounts significantly increased in the short-term treatment group. Dose-dependent rise of ampk in animals treated to 2AA suggest an increase production of hepatic ampk in response to the toxicity of 2AA in order to maintain cellular homeostasis. In contrast, the reduction in ampk concentration in treated animals within the 4-week set indicated an adaptive recovery